In this project we examine the thesis that aromatase, in concert with other androgenconverting enzymes in the brain, is an on-site regulatory system for determining the precise topographical distribution and local concentration of active hormone (estrogen), thereby modulating responses to circulating hormone (androgen). Changes in the amount of estrogen synthesized in discrete brain regions may account for differences in androgen feedback sensitivity and behavioral responsiveness that are associated with age, sex, and natural and photoperiod-regulated reproductive cycles. We are using 3H-androgen in an in vitro homogenate assay to recored changes in central aromatase, 5alpha-and 5beta-reductase activities in hamsters in relation to life cycle and reproductive rhythms. Specifically, we plan to: (1) determine the quantitative distribution of enzymes in microdissected brain regions and devise a standardized procedure for subsequent experiments: (2) measure activity in male and female brain from birth to sexual maturity; (3) compare brain activity in adult females in relation to the estrous cycle; (4) measure changes in adult males during natural seasonal cycles and (5) photoperiod-regulated cycles in the laboratory; (6) record changes in males and females in relation to diurnal rhythms; (7) in selected experimental groups, correlate results of in vitro assays with the quantity of receptor-bound estrogen following administration of androgen in vivo. If it is true that steriod metabolic enzymes in target areas of the brain are a fine-tuning mechanism controlling the availability of active hormone, a new approach to the diagnosis and treatment of neuroendocrine dysfunction and artificial control of fertility will be feasible.